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Molecular and Cellular Biology

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https://www.readbyqxmd.com/read/28096188/erk1-2-phosphorylate-gab2-to-promote-a-negative-feedback-loop-that-attenuates-pi3k-akt-signaling
#1
Xiaocui Zhang, Geneviève Lavoie, Antoine Méant, Léo Aubert, Marie Cargnello, André Haman, Trang Hoang, Philippe P Roux
The scaffolding adapter protein Gab2 (Grb2-associated binder) promotes cell proliferation, survival and motility by engaging several signaling pathways downstream of growth factor and cytokine receptors. In particular, Gab2 plays essential roles in mast cells as it is required for PI3K (phosphoinositide 3-kinase) activation in response to Kit and the high-affinity IgE receptor. While the positive role of Gab2 in PI3K signaling is well documented, very little is known about the mechanisms that attenuate its function...
January 17, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28069743/derepression-of-the-dna-methylation-machinery-of-gata1-gene-triggers-the-differentiation-cue-for-erythropoiesis
#2
Lei Yu, Jun Takai, Akihito Otsuki, Fumiki Katsuoka, Mikiko Suzuki, Saori Katayama, Masahiro Nezu, James Douglas Engel, Takashi Moriguchi, Masayuki Yamamoto
GATA1 is a critical regulator of erythropoiesis. While the mechanisms underlying the high-level expression of GATA1 in maturing erythroid cells have been studied extensively, the initial activation of the Gata1 gene in early hematopoietic progenitors remains to be elucidated. We previously identified a hematopoietic stem and progenitor cell (HSPC)-specific silencer element (the Gata1 methylation determining region; G1MDR) that recruits DNA methyltransferase 1 (Dnmt1) and provokes the methylation of the Gata1 gene enhancer...
January 9, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28069742/islet1-dependent-%C3%AE-catenin-hedgehog-signaling-is-required-for-outgrowth-of-the-lower-jaw
#3
Feixue Li, Guoquan Fu, Ying Liu, Xiaoping Miao, Yan Li, Xueqin Yang, Xiaoyun Zhang, Dongliang Yu, Lin Gan, Mengsheng Qiu, Yiping Chen, Ze Zhang, Zunyi Zhang
Mandibular patterning information initially resides in the epithelium during development. However, how transcriptional regulation of epithelial-derived signaling controls morphogenesis of the mandible remains elusive. Using Shh(Cre) to target the mandibular epithelium, we ablated transcription factor Islet1, resulting in a distally truncated mandible via unbalanced cell apoptosis and decreased cell proliferation in the distal mesenchyme. Loss of Islet1 caused a lack of cartilage at the distal tip, leading to the two growing mandibular elements to be fused surrounding the rostral process of Meckels cartilage...
January 9, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28069741/tor-complex-2-regulated-protein-kinase-fpk1-stimulates-endocytosis-via-inhibition-of-ark1-prk1-related-protein-kinase-akl1-in-saccharomyces-cerevisiae
#4
Françoise M Roelants, Kristin L Leskoske, Ross T A Pedersen, Alexander Muir, Jeffrey M-H Liu, Gregory C Finnigan, Jeremy Thorner
Depending on the stress, plasma membrane alterations activate or inhibit yeast Target of Rapamycin (TOR) Complex 2, which, in turn, upregulates or downregulates the activity of its essential downstream effector, protein kinase Ypk1. Through phosphorylation of multiple substrates, Ypk1 controls many processes that restore homeostasis. One such substrate is protein kinase Fpk1, which is negatively regulated by Ypk1. Fpk1 phosphorylates and stimulates flippases that translocate aminoglycerophospholipids from the outer to the inner leaflet of the plasma membrane...
January 9, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28069740/checkpoint-independent-regulation-of-origin-firing-by-mrc1-through-interaction-with-hsk1-kinase
#5
Seiji Matsumoto, Yutaka Kanoh, Michie Shimmoto, Motoshi Hayano, Kyosuke Ueda, Rino Fukatsu, Naoko Kakusho, Hisao Masai
Mrc1 is a conserved checkpoint mediator protein that transduces replication-stress signal to downstream effector kinase. Loss of mrc1 checkpoint activity results in aberrant activation of late/dormant origins in the presence of hydroxyurea. Mrc1 was also suggested to regulate orders of early-origin firing in a checkpoint-independent manner, but its mechanism was unknown. Here we identify HBS (Hsk1 Bypass Segment) on Mrc1. ΔHBS does not suppress late/dormant origin firing in the presence of hydroxyurea but causes precocious and enhanced activation of weak early-firing origins during normal S-phase progression, and bypasses the requirement of Hsk1 for growth...
January 9, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28069739/a-two-tiered-mechanism-enables-localized-cdc42-signaling-during-enterocyte-polarization
#6
Lucas J M Bruurs, Susan Zwakenberg, Mirjam C van der Net, Fried J Zwartkruis, Johannes L Bos
Signaling by the small GTPase Cdc42 governs a diverse set of cellular processes that contribute to tissue morphogenesis. Since these processes often require highly localized signaling, Cdc42 activity must be clustered in order to prevent ectopic signaling. During cell polarization, apical Cdc42 signaling directs the positioning of the nascent apical membrane. However, the molecular mechanisms that drive Cdc42 clustering during polarity establishment are largely unknown.Here we demonstrate that during cell polarization localized Cdc42 signaling is enabled via activity-dependent control of Cdc42 mobility...
January 9, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28069738/fbxl5-inactivation-in-mouse-brain-induces-aberrant-proliferation-of-neural-stem-progenitor-cells
#7
Takayoshi Yamauchi, Masaaki Nishiyama, Toshiro Moroishi, Atsuki Kawamura, Keiichi I Nakayama
FBXL5 is the substrate recognition subunit of an SCF-type ubiquitin ligase that serves as a master regulator of iron metabolism in mammalian cells. We previously showed that mice with systemic deficiency of FBXL5 fail to sense intracellular iron levels and die in utero at embryonic day (E) 8.5 as a result of iron overload and subsequent oxidative stress. This early embryonic mortality has thus impeded study of the role of FBXL5 in brain development. We have now generated mice lacking FBXL5 specifically in Nestin-expressing neural stem-progenitor cells (NSPCs) in the brain...
January 9, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28069737/mtorc1-plays-an-important-role-in-skeletal-development-by-controlling-pre-osteoblast-differentiation
#8
Stephen Fitter, Mary P Matthews, Sally K Martin, Jianling Xie, Soo Siang Ooi, Carl R Walkley, John D Codrington, Markus A Ruegg, Michael N Hall, Christopher G Proud, Stan Gronthos, Andrew C W Zannettino
The mammalian target of rapamycin complex 1 (mTORC1) is activated by extracellular factors that control bone accrual. However, the direct role of this complex in osteoblast biology remains to be determined. To investigate this question, we disrupted mTORC1 function in pre-osteoblasts by targeted deletion of Raptor (Rptor) in Osterix-expressing cells. Deletion of Rptor resulted in reduced limb length that was associated with smaller epiphyseal growth plates in the postnatal skeleton. Rptor deletion caused a marked reduction in pre- and post-natal bone accrual, which was evident in skeletal elements derived from both intramembranous and endochondrial ossification...
January 9, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28052936/klhl3-knockout-mice-reveal-the-physiological-role-of-klhl3-and-the-pathophysiology-of-phaii-caused-by-mutant-klhl3
#9
Emi Sasaki, Koichiro Susa, Takayasu Mori, Kiyoshi Isobe, Yuya Araki, Yuichi Inoue, Yuki Yoshizaki, Fumiaki Ando, Yutaro Mori, Shintaro Mandai, Moko Zeniya, Daiei Takahashi, Naohiro Nomura, Tatemitsu Rai, Shinichi Uchida, Eisei Sohara
Mutations in the with-no-lysine kinase 1 (WNK1), WNK4, kelch-like 3 (KLHL3), and cullin3 (CUL3) genes are known to cause the hereditary disease pseudohypoaldosteronism type II (PHAII). It was recently demonstrated that this results from the defective degradation of WNK1 and WNK4 by the KLHL3/CUL3 ubiquitin ligase complex. However, the other physiological in vivo roles of KLHL3 remain unclear. Therefore, here we generated KLHL3(-/-) mice that expressed β-galactosidase (β-gal) under the endogenous KLHL3 promoter...
January 4, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28052935/d120-and-k152-within-the-ph-domain-of-t-cell-adapter-skap55-regulate-plasma-membrane-targeting-of-skap55-and-lfa-1-affinity-modulation-in-human-t-lymphocytes
#10
Amelie Witte, Bernhard Meineke, Jana Sticht, Lars Philipsen, Benno Kuropka, Andreas J Müller, Christian Freund, Burkhart Schraven, Stefanie Kliche
The β2-integrin lymphocyte function-associated antigen-1 (LFA-1) is needed for T cell receptor (TCR) induced activation of LFA-1 to promote T cell adhesion and interaction with antigen presenting cells (APCs). LFA-1-mediated cell-cell interactions are critical for proper T cell differentiation and proliferation. The Src Kinase-Associated Phosphoprotein of 55 kDa (SKAP55) is a key regulator of TCR-mediated LFA-1 signaling (inside-out/outside-in signaling). To gain understanding of how SKAP55 controls TCR-mediated LFA-1 activation, we assessed the functional role of its Pleckstrin Homology (PH) domain...
January 4, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28031331/activation-dependent-traf3-exon-8-alternative-splicing-is-controlled-by-celf2-and-hnrnp-c-binding-to-an-upstream-intronic-element
#11
Astrid-Solveig Schultz, Marco Preußner, Mario Bunse, Rotem Karni, Florian Heyd
Cell-type specific and inducible alternative splicing has a fundamental impact on regulating gene expression and cellular function in a variety of settings including activation and differentiation. We have recently shown that activation-induced skipping of TRAF3 exon 8 activates non-canonical NFkB signaling upon T cell stimulation, but the regulatory basis for this splicing event remains unknown. Here we identify cis- and trans-regulatory elements rendering this splicing switch activation-dependent and cell-type specific...
December 28, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28031330/setd4-regulates-cell-quiescence-and-catalyzes-the-trimethylation-of-h4k20-during-diapause-formation-of-artemia
#12
Li Dai, Sen Ye, Hua-Wei Li, Dian-Fu Chen, Hong-Liang Wang, Sheng-Nan Jia, Cheng Lin, Jin-Shu Yang, Fan Yang, Hiromichi Nagasawa, Wei-Jun Yang
As a prominent characteristic of cell life, the regulation of cell quiescence is important for proper development, regeneration, and stress resistance, and may play a role in certain degenerative diseases. However, the mechanism underlying quiescence remains largely unknown. Encysted embryos of Artemia are useful for studying the regulation of this state because they remain quiescent for prolonged periods during diapause, a state of obligate dormancy. In the present study, SET domain-containing protein 4, a histone lysine methyltransferase, was identified and characterized from Artemia and named as Ar-SETD4...
December 28, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28031329/hur-enhances-early-restitution-of-the-intestinal-epithelium-by-increasing-cdc42-translation
#13
Lan Liu, Ran Zhuang, Lan Xiao, Hee Kyoung Chung, Jason Luo, Douglas J Turner, Jaladanki N Rao, Myriam Gorospe, Jian-Ying Wang
The mammalian intestinal mucosa exhibits a spectrum of responses after acute injury and repairs itself rapidly to restore the epithelial integrity. The RNA-binding protein HuR regulates the stability and translation of target mRNAs and is involved in many aspects of gut epithelium homeostasis, but its exact role in the regulation of mucosal repair after injury remains unknown. Here we show that HuR is essential for early intestinal epithelial restitution by increasing the expression of cell division control protein 42 (Cdc42) at the posttranscriptional level...
December 28, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28031328/interactome-analysis-reveals-a-novel-role-for-rad6-in-the-regulation-of-proteasome-activity-and-localization-in-response-to-dna-damage
#14
Hongli An, Lu Yang, Chen Wang, Zhixue Gan, Haihui Gu, Tao Zhang, Xin Huang, Yan Liu, Yufeng Li, Shing-Jyh Chang, Jianghua Lai, Ya-Bin Li, Su Chen, Fang-Lin Sun
RAD6, an E2 ubiquitin-conjugating enzyme, is a key node for determining different DNA damage repair pathways, controlling both the "error-prone" and "error-free" DNA damage repair pathways through differentially regulating the ubiquitination of the proliferating cell nuclear antigen (PCNA) protein. However, whether other pathways are involved in the RAD6-mediated regulation of DNA damage repair is still unclear. To deeply understand the molecular mechanisms of RAD6 in DNA damage repair, we performed a proteomic analysis and identified the changes of the protein-protein interaction (PPI) networks of RAD6 before and after X-ray irradiation...
December 28, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28031327/inpp5e-preserves-genomic-stability-through-regulation-of-mitosis
#15
Elizabeth A Sierra Potchanant, Donna Cerabona, Zahi Abdul Sater, Ying He, Zejin Sun, Jeff Gehlhausen, Grzegorz Nalepa
The partially understood phosphoinositide signaling cascade regulates multiple aspects of cellular metabolism. Previous studies revealed that INPP5E, the inositol polyphosphate-5-phosphatase mutated in the developmental disorders Joubert and MORM syndromes, is essential for the function of the primary cilium and maintenance of phosphoinositide balance in non-dividing cells. Here, we report that INPP5E further contributes to cellular homeostasis by regulating cell division. We found that silencing or genetic knockout of INPP5E in human and murine cells impairs the spindle assembly checkpoint, centrosome and spindle function, and maintenance of chromosomal integrity...
December 28, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28031326/myocyte-derived-hsp90-modulates-collagen-upregulation-via-biphasic-activation-of-stat-3-in-fibroblasts-during-cardiac-hypertrophy
#16
Ritwik Datta, Trisha Bansal, Santanu Rana, Kaberi Datta, Ratul Datta Chaudhuri, Mamta Chawla-Sarkar, Sagartirtha Sarkar
Signal transducer and activator of transcription-3 (STAT-3) mediated signalling in relation to upregulated collagen expression in fibroblasts is well defined during cardiac hypertrophy. Recent findings from our laboratory have identified Heat shock protein 90 (Hsp90) as a critical modulator of fibrotic signalling in cardiac fibroblasts in this disease milieu. The present study was therefore intended to analyze the role of Hsp90 in the STAT-3 mediated collagen upregulation process. Our data revealed a significant difference between in vivo and in vitro results pointing to a possible involvement of myocyte-fibroblast crosstalk in this process...
December 28, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27994014/human-ap-endonuclease-ape1-is-acetylated-at-dna-damage-sites-in-chromatin-and-acetylation-modulates-its-dna-repair-activity
#17
Shrabasti Roychoudhury, Somsubhra Nath, Heyu Song, Muralidhar L Hegde, Larry J Bellot, Anil K Mantha, Shiladitya Sengupta, Sutapa Ray, Amarnath Natarajan, Kishor K Bhakat
Apurinic/apyrimidinic (AP) sites, the most frequently formed DNA lesions in the genome, inhibit transcription and block replication. The primary enzyme to repair AP sites in mammalian cells is the AP endonuclease (APE1), which functions through the Base Excision Repair (BER) pathway. Although the mechanism by which APE1 repairs AP sites in vitro has been extensively investigated, it is largely unknown how APE1 repairs AP sites in cells. Here, we show that APE1 is acetylated (AcAPE1) after binding to the AP sites in chromatin and that AcAPE1 is exclusively present on chromatin throughout the cell cycle...
December 19, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27994013/role-of-tim17-transmembrane-regions-in-regulating-the-architecture-of-presequence-translocase-and-mtdna-stability
#18
Srujan Kumar Matta, Gautam Pareek, Kondalarao Bankapalli, Anjaneya O, Patrick D'Silva
Mitochondrial life-cycle and protein import are intricate cellular processes, which require precise coordination between transport machineries of outer and inner mitochondrial membranes. Presequence translocase performs indispensable function of translocating preproteins having N-terminal targeting sequences across the inner membrane. Tim23 forms the core of voltage gated import channel, while Tim17 is presumed to maintain the stoichiometry of the translocase. However, mechanistic insights into how Tim17 coordinates these regulatory events within the complex remained elusive...
December 19, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27994012/asymmetric-arginine-dimethylation-modulates-mitochondrial-energy-metabolism-and-homeostasis-in-caenorhabditis-elegans
#19
Liang Sha, Hiroaki Daitoku, Sho Araoi, Yuta Kaneko, Yuta Takahashi, Koichiro Kako, Akiyoshi Fukamizu
Protein Arginine Methyltransferase 1 (PRMT1) catalyzes asymmetric arginine dimethylation on cellular proteins and modulates various aspects of biological processes, such as signal transduction, DNA repair, and transcriptional regulation. We have previously reported that the null mutant of prmt-1 in C. elegans exhibits a slightly short lifespan, but the physiological significances of PRMT-1 remains largely unclear. Here we explored the role of PRMT-1 on mitochondrial function as hinted by a two-dimensional Western blot-based proteomic study...
December 19, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27994011/the-role-of-cwc24-in-the-first-catalytic-step-of-splicing-and-fidelity-of-5-splice-site-selection
#20
Nan-Ying Wu, Che-Sheng Chung, Soo-Chen Cheng
Cwc24 is an essential splicing factor, but only transiently associates with the spliceosome with an unknown function. The protein contains a RING-finger and a zinc-finger domain in the carboxyl terminus. The human ortholog of Cwc24, RNF113A, has been associated with the disorder trichothiodystrophy. Here, we show that the zinc-finger domain is essential for Cwc24 function, while the RING-finger domain is dispensable. Cwc24 binds to the spliceosome after the Prp19-associated complex, and is released upon Prp2 action...
December 19, 2016: Molecular and Cellular Biology
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